RESUMEN
Atopic dermatitis is a cutaneous inflammatory disease characterized by intense pruritus, which is often underestimated despite its direct impact on patients' health-related quality of life and the high burden it poses. The authors' goal was to design a qualitative tool to guide patients and healthcare professionals in their assessment and interpretation of pruritus intensity using a numerical rating scale. The draft of this tool, henceforth "guideline", was developed based on a systematic literature review and focus groups comprising patients and a scientific committee. This draft was validated with an independent group of patients and the final version was designed following their feedback. According to the results of the systematic review, pruritus impacts 6 health-related quality of life domains: sleep quality; emotional status; overall health-related quality of life; physical function; social/sexual activity; productivity, particularly affecting sleep quality and the emotional domain. Patients considered that physical function was the most strongly affected domain, followed by sleep quality and emotional well-being, establishing that a minimum pruritus intensity of 4 and 7 points impacts moderately and severely, respectively, on the different domains of patients' health- related quality of life. The guideline may help patients and healthcare professionals to interpret and assess pruritus intensity using a numerical rating scale and to understand the impact of pruritus on patients' health-related quality of life.
Asunto(s)
Dermatitis Atópica , Prurito , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Prurito/psicología , Prurito/diagnóstico , Prurito/etiología , Prurito/fisiopatología , Dermatitis Atópica/psicología , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Sueño , Emociones , Femenino , Masculino , Reproducibilidad de los Resultados , Adulto , Grupos Focales , Valor Predictivo de las Pruebas , Investigación Cualitativa , Costo de Enfermedad , Encuestas y Cuestionarios , Persona de Mediana EdadRESUMEN
Nilotinib is a new multitargeted tyrosine kinase inhibitor, which is used to treat chronic myelogenous leukemia when intolerance or recurrence to imatinib occurs. We report the case of a 14-year-old patient being treated with nilotinib who developed a keratosis pilaris-like eruption. This cutaneous adverse effect is a rare but increasingly reported side effect of this therapy.
Asunto(s)
Anomalías Múltiples , Enfermedad de Darier , Cejas/anomalías , Adolescente , Antineoplásicos , Proteínas de Fusión bcr-abl , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversosRESUMEN
Mosaicism denotes an individual who has at least two populations of cells with distinct genotypes that are derived from a single fertilized egg. Genetic variation among the cell lines can involve whole chromosomes, structural or copy-number variants, small or single-nucleotide variants, or epigenetic variants. The mutational events that underlie mosaic variants occur during mitotic cell divisions after fertilization and zygote formation. The initiating mutational event can occur in any types of cell at any time in development, leading to enormous variation in the distribution and phenotypic effect of mosaicism. A number of classification proposals have been put forward to classify genetic mosaicism into categories based on the location, pattern, and mechanisms of the disease. We here propose a new classification of genetic mosaicism that considers the affected tissue, the pattern and distribution of the mosaicism, the pathogenicity of the variant, the direction of the change (benign to pathogenic vs. pathogenic to benign), and the postzygotic mutational mechanism. The accurate and comprehensive categorization and subtyping of mosaicisms is important and has potential clinical utility to define the natural history of these disorders, tailor follow-up frequency and interventions, estimate recurrence risks, and guide therapeutic decisions.
Asunto(s)
Variaciones en el Número de Copia de ADN , Mosaicismo , Análisis Mutacional de ADN , Humanos , Mutación , Programas InformáticosRESUMEN
Capillary malformation-arteriovenous malformation (CM-AVM) is caused by germline RASA1 and EPHB4 alterations. RASA1 intralesional second hits have also been reported. Here we report RASA1 constitutional mosaicism, defined here as the presence of a mosaic variant in all cell types of an individual, in two patients with CM-AVM. High-throughput sequencing was used to search for RASA1 pathogenic variants in blood samples from two unrelated patients with CM-AVM. An affected tissue sample from one of the patients was also analyzed. Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. Constitutional mosaicism has implications for accurate molecular diagnosis and recurrence risk and helps to explain the great phenotypic variability in CM-AVM.
Asunto(s)
Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/genética , Capilares/anomalías , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mosaicismo , Mutación , Mancha Vino de Oporto/diagnóstico , Mancha Vino de Oporto/genética , Proteína Activadora de GTPasa p120/genética , Alelos , Sustitución de Aminoácidos , Angiografía por Tomografía Computarizada , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Humanos , MasculinoRESUMEN
A newborn boy presented with a progressively infiltrating and painful congenital ulcerated plaque on the back of his left foot. A partial excision was performed and histopathologic examination confirmed a diagnosis of a plexiform fibrohistiocytic tumor. This rare tumor usually appears in children and adolescents, with congenital presentations even more uncommon. This case details the exceptional presentation of a congenital ulcerated plexiform fibrohistiocytic tumor with a review of the current literature.
Asunto(s)
Histiocitoma Fibroso Benigno/patología , Neoplasias Cutáneas/patología , Neoplasias de los Tejidos Blandos/patología , Pie/patología , Humanos , Recién Nacido , Masculino , Úlcera Cutánea/patologíaRESUMEN
African tick-bite fever (ATBF), a tickborne disease endemic in rural areas of sub-Saharan Africa and the West Indies caused by Rickettsia africae, has been recognized as an emerging health problem in recent years. ATBF has been reported as the second most commonly documented etiology of fever, after malaria, in travelers who return ill from sub-Saharan Africa. Most cases reported in the literature occurred in middle-aged adults, so the incidence of ATBF in children is unclear. We report a cluster of three cases of ATBF that occurred in children ages 7 to 16 years after returning from a game-hunting safari in South Africa.
Asunto(s)
Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Rickettsiosis Exantemáticas/diagnóstico , Adolescente , Niño , Fiebre/etiología , Humanos , Masculino , Rickettsia , Úlcera Cutánea/etiología , Sudáfrica , Rickettsiosis Exantemáticas/tratamiento farmacológico , ViajeRESUMEN
Notalgia paresthetica is characterized by a hyperpigmented macular pruritic skin lesion most commonly localized unilaterally in the middle and upper back region. This condition has been reported in association with multiple endocrine neoplasia syndrome type 2A (MEN 2A) in several families; it rarely affects children and it may serve as an early marker of MEN 2A. We report a 9-year-old girl diagnosed with MEN 2A and notalgia paresthetica.
Asunto(s)
Hiperpigmentación/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Niño , Femenino , Humanos , Hiperpigmentación/complicaciones , Neoplasia Endocrina Múltiple Tipo 2a/complicacionesRESUMEN
OBJECTIVE: To evaluate the efficacy of 1% topical cidofovir cream for the treatment of anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals. DESIGN: Single-arm, open-label, pilot clinical trial. METHODS: The study medication was applied intraanally three times per week for 4 weeks. Lesions were assessed with high-resolution anoscopy and biopsy at weeks 12 and 24. The primary endpoint was complete remission (CR) at week 12, defined as clinical and histological remission. We also evaluated partial remission defined as regression to low-grade squamous intraepithelial lesion. RESULTS: We included 17 HIV-infected patients with intraanal HSIL. Median (interquartile range) age was 36 years (28-41), median (interquartile range) CD4 cell count was 545âcells/µl (358-630), and viral load was less than 50 âcopies/ml in 93.7%. Two patients were lost to follow-up, one of them did not apply treatment. At 12 weeks, in the intention-to-treat population, 10 out of 16 patients [62.5%; 95% confidence interval (CI), 38.2-85.7%] had achieved CR. At 24 weeks, seven of the 10 patients (70%; 95% CI, 47-93%) remained in CR, but two out of 10 patients (20%; 95% CI, 0-40%) presented HSIL. One patient did not attend the visit at 24 weeks. Three patients with persistent HSIL at 12 weeks improved at 24 weeks (partial response in one and CR in two). The mean number of human papillomavirus genotypes decreased from 5.2 to 2.7 at 12 weeks (Pâ=â0.002). Local adverse effects were frequent (81%), although there were no discontinuations because of adverse events. CONCLUSION: One percent topical cidofovir could be an appropriate alternative therapy in HIV-infected patients with anal HSIL. CLINICAL TRIAL: gov unique identifier: NCT01946009.
Asunto(s)
Antivirales/administración & dosificación , Neoplasias del Ano/tratamiento farmacológico , Carcinoma in Situ/tratamiento farmacológico , Citosina/análogos & derivados , Infecciones por VIH/complicaciones , Organofosfonatos/administración & dosificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/tratamiento farmacológico , Administración Tópica , Adulto , Biopsia , Cidofovir , Citosina/administración & dosificación , Humanos , Masculino , Proyectos Piloto , Resultado del TratamientoRESUMEN
Trichodysplasia spinulosa (TS) is a rare entity, characterized by a follicular digitate keratosis predominantly affecting the face and variable degrees of hair loss, most severely facial hair, that occurs in immunosuppressed individuals, and is considered to be a viral infection caused by a human polyomavirus, the "TS-associated polyomavirus." Histologically it is characterized by hair follicles with excessive inner root-sheath differentiation and intraepithelial viral inclusions. Correlation of these findings with clinical features is required for diagnosis. Treatment with antiviral agents appears to be the most effective. We report the occurrence of TS in a 20-month-old girl with multivisceral transplantation due to short-bowel syndrome secondary to intestinal atresia and gastroschisis. The patient was treated with cidofovir 1% cream, with significant improvement and without any adverse effects. We describe the youngest patient, to our knowledge, with TS.
Asunto(s)
Antivirales/uso terapéutico , Citosina/análogos & derivados , Enfermedades del Cabello/diagnóstico , Organofosfonatos/uso terapéutico , Poliomavirus , Administración Tópica , Antivirales/administración & dosificación , Cidofovir , Citosina/administración & dosificación , Citosina/uso terapéutico , Femenino , Enfermedades del Cabello/tratamiento farmacológico , Enfermedades del Cabello/virología , Folículo Piloso , Humanos , Huésped Inmunocomprometido , Lactante , Organofosfonatos/administración & dosificaciónRESUMEN
Little is known about the incidence and management of dermatofibrosarcoma protuberans (DFSP) in children. We conducted a retrospective review of all patients younger than 18 years of age treated for DFSP over a period of 11 years (2000-2011) in Madrid, Spain. The sample consisted of 13 children. The average annual incidence of DFSP in the pediatric population corresponded to 1.02 cases per million person-years (95% confidence interval 0.55, 1.73). Sites of involvement were diverse, with 15.3% of tumors found in acral locations. The median tumor size was 3.5 cm × 3 cm and the median time from apparent onset to diagnosis was 36 months. Histopathologic examination revealed conventional (77.0%), pigmented (15.4%), and myxoid (7.6%) variants. The mitotic index was consistently <5 per 10 high-power fields. All lesions were removed using surgical excision. One patient developed a local recurrence because of initial affected margins; none developed metastases. The median duration of clinical follow-up was 70.5 months. This study estimated the average annual incidence rate of DFSP in a population of patients younger than 18 years and reviewed the experience of several hospitals in the management of this tumor.
Asunto(s)
Dermatofibrosarcoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Niño , Dermatofibrosarcoma/diagnóstico , Dermatofibrosarcoma/terapia , Femenino , Humanos , Incidencia , Lactante , Masculino , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , España/epidemiologíaRESUMEN
BACKGROUND: Solar radiation should be avoided in melanoma patients. Nevertheless, this is the main means by which the body produces vitamin D. Evidence suggests a protective role against cancer for vitamin D. Since vitamin D performs its function by binding the receptor encoded by the vitamin D-receptor gene (VDR), most studies have focused on polymorphisms (SNPs) within this gene. However, the gene encoding the vitamin D-binding protein (GC) appears in recent studies as a major player in the role of a serum vitamin D level regulator and in Cutaneous Melanoma (CM) predisposition. METHODS: We performed a case-control study of 12 polymorphisms on GC and 9 on VDR among 530 cases and 314 controls from Spanish population. RESULTS: We found association between SNP rs12512631, located 3'downstream of GC, and risk of CM that seems to fit a dominant model (OR 1.63 95%CI 1.23-2.17 p-value 7×10(-4)). This association remained Bonferroni's correction and after adjustment for potential confounders (p-value 3×10(-3)) and even after increasing the sample size to 1729 individuals (p-value 0.0129). Moreover, we confirmed evidence of an association between CM susceptibility and the linkage disequilibrium block marked by tag-SNP rs222016 (p-value 0.032). This block covers the GC intron 1 region, with probable regulatory functions. CONCLUSION: To our knowledge, this is the first vitamin D pathway-related polymorphism study in melanoma risk conducted in the Spanish population. Furthermore, we show an association between polymorphisms in GC and melanoma risk, confirming recent studies in different populations.
Asunto(s)
Predisposición Genética a la Enfermedad , Melanoma/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias Cutáneas/genética , Proteína de Unión a Vitamina D/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Haplotipos/genética , Humanos , Masculino , Fenotipo , Factores de Riesgo , EspañaRESUMEN
BACKGROUND: Dystrophic Epidermolysis Bullosa (DEB) is a rare genodermatosis (7 cases per million) that causes blisters and erosions with minor trauma in skin and mucosa, and other systemic complications. A recently updated systematic review showed that the research evidence about DEB therapies is poor. As new trials in DEB are difficult and expensive, it is important to prioritizise research that patients and clinicians consider more relevant. OBJECTIVES: To describe and prioritize the most important uncertainties about DEB treatment shared by patients, carers and health care professionals (HCPs) in order to promote research in those areas. METHODS: A DEB Priority Setting Partnership (PSP) was established, including patients, carers and HCPs. DBE uncertainties were gathered from patients and clinicians, and prioritized in a transparent process, using the methodology advocated by the James Lind Alliance. RESULTS: In the consultation stage, 323 uncertainties were submitted by 58 participants. Once the duplicated and non-treatment uncertainties were removed, the remainder were reduced to a list of 24 most voted questions. These 24 uncertainties were prioritized in a final workshop where a balanced number of patients, carers and HCPs selected the top 10 therapy uncertainties. The final list includes interventions in wound care, itch and pain management, treatment and prevention of syndactyly, cancer prevention and future promising therapies. CONCLUSIONS: The final list of the top 10 treatment uncertainties on the management of DEB provides guidance for researchers and funding bodies, to ensure that future research answers questions that are important to both clinicians and patients. The method proposed by the James Lind Alliance is feasible for very rare disorders.
Asunto(s)
Epidermólisis Ampollosa Distrófica/terapia , Prioridades en Salud , Incertidumbre , HumanosRESUMEN
We describe the clinical, histopathologic, immunohistochemical, and molecular findings in an additional case of lipoatrophic panniculitis selectively involving the ankles in a 12-year-old boy. This idiopathic, rarely reported entity is presumed to have an autoimmune pathogenesis. Histological findings are a lipophagic lobular panniculits, that in our case featured focally increased numbers of lymphocytes rimming the adipocytes, and infiltration of vascular walls by mildly atypical lymphoid cells, raising the differential diagnosis of subcutaneous panniculitis-like T-cell lymphoma.
Asunto(s)
Enfermedades del Tejido Conjuntivo/diagnóstico , Linfoma de Células T/diagnóstico , Paniculitis/diagnóstico , Neoplasias Cutáneas/diagnóstico , Grasa Subcutánea/patología , Adipocitos/patología , Tobillo , Atrofia , Niño , Diagnóstico Diferencial , Humanos , Masculino , Paniculitis/tratamiento farmacológicoRESUMEN
Actinic lichen planus (ALP) is a photosensitive variant of lichen planus, affecting mainly young adults of Middle Eastern descent. We report a case of ALP in a 9-year-old Colombian girl with an excellent response to hydroxychloroquine and photoprotection.
Asunto(s)
Antimaláricos/uso terapéutico , Dermatosis Facial/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Liquen Plano/tratamiento farmacológico , Trastornos por Fotosensibilidad/tratamiento farmacológico , Niño , Dermatosis Facial/patología , Femenino , Humanos , Liquen Plano/patología , Trastornos por Fotosensibilidad/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete. OBJECTIVES: We sought to describe the prevalence of ARCI. METHODS: We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method. RESULTS: We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association. LIMITATIONS: The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries. CONCLUSIONS: The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study.
Asunto(s)
Bases de Datos Factuales/estadística & datos numéricos , Eritrodermia Ictiosiforme Congénita/epidemiología , Ictiosis Lamelar/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Métodos Epidemiológicos , Femenino , Humanos , Eritrodermia Ictiosiforme Congénita/genética , Ictiosis Lamelar/genética , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Derivación y Consulta/estadística & datos numéricos , España/epidemiología , Adulto JovenRESUMEN
We report an exceptional case of umbilical basal cell carcinoma (BCC) in a 21-year-old man, whose correct diagnosis was suggested by dermoscopy during initial complete body mole mapping. Although BCC is a common skin tumor, only 7 cases of BCC arising within the umbilicus have been reported previously. To the best of our knowledge, our patient is unique because of his age, being the youngest case of umbilical BCC described in the literature. Complete examination and digital dermoscopic monitoring let us identify an asymptomatic, nonpigmented papule at the umbilicus. Dermoscopy images revealed signs of superficial ulceration and several types of vascular structures, which gave us the clue for the diagnosis and helped us differentiate it from other lesions such as Spitz nevus or amelanotic melanoma. The diagnosis was confirmed with histopathology after excision and there was no evidence of relapse in the following four years.
Asunto(s)
Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología , Carcinoma Basocelular/diagnóstico , Dermoscopía , Humanos , Masculino , Neoplasias Primarias Múltiples , Nevo Pigmentado/patología , Neoplasias Cutáneas/diagnóstico , Ombligo , Adulto JovenRESUMEN
Laugier-Hunziker syndrome (LHS) is an acquired, benign, macular hyperpigmentation of the lips and oral mucosa, often associated with pigmentation of the nails. Volar acral maculae on the palms and fingertips of patients affected by LHS are a typical feature of this rare entity. Dermoscopic examination of these maculae has been described in a previous report, in which authors found a parallel-furrow pattern. We describe two cases in which a parallel-ridge pattern (PRP) was found on the dermoscopic examination of the pigmented acral lesions. Histological examination showed increased melanin in basal keratinocytes, which was most prominent in those located at the crista intermedia profunda, that is, in the epidermal rete ridges underlying the surface ridges. In our study, dermoscopic features of the pigmented maculae found on LHS differed from those previously described. In addition, by means of this case report, the histological features of these lesions are described for the first time, showing an excellent correlation with dermoscopy. The reported cases prove that although the PRP is very specific of melanoma, it is also possible to find it in benign lesions. Therefore, we must be familiar with the differential diagnosis of PRP, and take into consideration the clinical context in which we find it. Further studies are needed to increase our knowledge on the histological and dermoscopic features of acral pigmented maculae of LHS.
Asunto(s)
Dermoscopía , Dermatosis de la Mano/patología , Hiperpigmentación/patología , Anciano , Diagnóstico Diferencial , Femenino , Dedos , Humanos , Enfermedades de los Labios/patología , Persona de Mediana Edad , Mucosa Bucal/patología , Uñas/patología , SíndromeRESUMEN
The CDKN2A gene is regarded as the major familial malignant melanoma (MM) susceptibility gene. Human pigmentation is one of the main modulators of individual risk of developing MM. Therefore, the genes involved in the determination of skin colour and tanning response are potentially implicated in MM predisposition and may be useful predictors of MM risk in the general population. The human melanocortin-1 receptor gene (MC1R) plays a crucial role in pigmentation and also appears to be important in MM. The OCA2 gene has emerged as a new and significant determinant of human iris colour variation. We present a case-control study in Spanish population including 390 consecutive patients with melanoma and 254 control subjects. Sequence analysis of the entire coding region and genotyping of 5 tag-SNPs in the genomic region of MC1R was performed. We identified 27 variants, two reaching statistical significance [R160W (OR: 4.18, 95% CI: 1.24-14.04, P = 0.02) and D294H (OR: 3.10, 95% CI: 1.37-7.01, P = 0.01)] and we detected two novel non-synonymous changes: V92L and T308M. Odds ratio for carrying two functional variants was 4.25 (95% CI: 2.30-7.84, P = 3.63 x 10(-6)). Haplotypes of the entire MC1R region have been established, and we observed an enrichment of a rare European haplotype similar to African values carrying variants V92M and I155T. In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles. We found that the variant allele A > G of OCA2/HERC2 (rs12913832) was associated with pigmentation features: eye, hair and skin colour; P-values = 1.8 x 10(-29), 9.2 x 10(-16), 1.1 x 10(-3), respectively, validating previous results.